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Abstract：
Congenital myasthenic syndrome (CMS) is an uncommon inherited neuromuscular junction disease. The clinical presentation of this disorder is diverse. Typically patients with this disorder present with early-onset swallowing difficulty and apnea in infancy, fluctuating ocular palsies and fatigable proximal muscle weakness during childhood, and late-onset form involving progressive weakness in adulthood. Difficulty in performing neurophysiology studies in children and the absence of a pathognomonic investigation marker increase the challenges in diagnosis of this disorder. The emergence of next-generation sequencing technology has circumvented these challenges somewhat, and has contributed to the discovery of novel mutations. We present here diagnostic odyssey of three CMS patients from two unrelated Kadazandusun kinships and their follow-up treatment. A rare homozygous mutation c.916G > C (p.Val306Leu) in CHAT gene was found in two siblings born of a consanguineous marriage. Third patient had compound heterozygous mutations c.406G > A (p.Val136Met) and c.916G > C (p.Val306Leu) in CHAT gene. We postulate that p.Val306Leu may be a founder mutation in the Kadazandusuns, an indigenous ethnic minority of Borneo Island.
摘要：
先天性肌无力综合征（CMS）是一种罕见的遗传性神经肌肉接头疾病。这种疾病的临床表现是多种多样的。通常，这种疾病的患者在婴儿期表现为早发性吞咽困难和呼吸暂停，儿童时期的波动性眼瘫和易疲劳的近端肌无力，以及涉及成年后进行性虚弱的迟发性形式。在儿童中进行神经生理学研究的困难以及缺乏病理标记的研究增加了该疾病诊断的挑战。新一代测序技术的出现在一定程度上规避了这些挑战,并有助于发现新的突变。我们在这里介绍了来自两个无关的Kadazandusun亲属关系的三名CMS患者的诊断冒险之旅及其后续治疗。罕见的纯合突变c.916G>C（p。在CHAT基因中的Val306Leu）在两个近亲婚姻中发现。第三名患者具有复合杂合突变c.406G>A（p。Val136Met）和c.916G>C（p。Val306Leu)在CHAT基因中。我们假设p.Val306Leu可能是Kadazandusns的创始人突变，婆罗洲岛的土著少数民族。
